In this project we are coupling genetic and environmental studies in selected families and twin pairs with disorders such as multiple sclerosis, Parkinson's disease, and Alzheimer's disease, in an effort to distinguish specific contributing factors. A multi-disciplinary study of 41 monozygotic twin pairs and 19 dizygotic twin pairs, selected on the basis of at least one member being diagnosed as having Parkinson's disease has led to the novel hypothesis that at least some cases are due to a reduced number of critical neurons in the substantia nigra and related structures very early in life. An hereditary leukoencephalopathy simulating MS with onset at about age 35 is under study in kindred with over 20 affected. Derangement of the autonomic nervous system is often seen early in the course and when recognized, serves to distinguish this single gene disorder from multiple sclerosis clinically. Computerized tomographic scan changes of the brain are dramatic.